Abstract

We combined systematic bioinformatics analyses and molecular dynamics simulations to assess the conservation patterns of Ser and Thr motifs in membrane proteins, and the effect of such motifs on the structure and dynamics of α-helical transmembrane (TM) segments. We find that Ser/Thr motifs are often present in β-barrel TM proteins. At least one Ser/Thr motif is present in almost half of the sequences of α-helical proteins analyzed here. The extensive bioinformatics analyses and inspection of protein structures led to the identification of molecular transporters with noticeable numbers of Ser/Thr motifs within the TM region. Given the energetic penalty for burying multiple Ser/Thr groups in the membrane hydrophobic core, the observation of transporters with multiple membrane-embedded Ser/Thr is intriguing and raises the question of how the presence of multiple Ser/Thr affects protein local structure and dynamics. Molecular dynamics simulations of four different Ser-containing model TM peptides indicate that backbone hydrogen bonding of membrane-buried Ser/Thr hydroxyl groups can significantly change the local structure and dynamics of the helix. Ser groups located close to the membrane interface can hydrogen bond to solvent water instead of protein backbone, leading to an enhanced local solvation of the peptide.

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Electronic supplementary material

The online version of this article (doi:10.1007/s00232-012-9452-4) contains supplementary material, which is available to authorized users.

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Acknowledgements

This research was supported in part by Grant GM-74637 from the National Institute of General Medical Sciences (to S.H.W), the Spanish Ministerio de Ciencia e Innovación (project TIN-2009-13950), the Consejería de Innovación, Investigación y Ciencia de la Junta de Andalucía (project TIC-02788) (to C.M.D.V.), the Marie Curie International Reintegration Award IRG276920/Biol-Transp-Comput (to A.-N.B), and an allocation of computer time from the National Science Foundation through the TeraGrid resources.